Specific tissue cells in general and spermatozoa in particular possess cell specific macromolecules. These presumably contribute to specific cell function; reproduction in the case of sperm. Such sperm specific macromolecules can incite auto and isoimmunity in males and females respectively. The resulting auto and isoantibodies can serve as probes to localize (e.g. immunoflourescence, immunoelectron microscopy), to isolate (e.g., affinity chromatography) and to test for reproductive function (inhibiting action of Fab antibodies in in vitro and in vivo insemination) of such auto and isoantigenic macromolecules. Finally, isoimmunity to sperm can produce female infertility dramatically. This implies one or more sperm isoantigens with antifertility vaccine properties. We are now engaged in the direct approach of isolating the active antifertility isoantigen(s) from sperm extracts known to contain antifertility vaccine action (Munoz and Metz, 1978). The current series of animals being isoimmunized with whole sperm and DEAE fractions of sperm extracts should yield sufficient isoantisera from "immunologically infertile" females to perform large scale isoantigen isolation by affinity chromatography. Localization and characterization of the isoantigens will be continued using these and other antisperm sera.